Total Sleep Deprivation Response in Major Depressive Disorder

UCLA Clinical Research Study (IRB #15-000856)

We are recruiting participants for a research study being conducted at UCLA. Research studies are voluntary and include only people who choose to take part, and who meet all of the eligibility criteria as determined by the study investigators.

Study Description


The purpose of this study is to examine how total sleep deprivation might work in the treatment of depression. In this study, sleep deprivation means you will be asked to remain awake for at least 23 hours, under continual observation. We cannot know if any individual patient will respond to sleep deprivation when used for depression.

We will study how sleep deprivation affects brain chemistry and function by collecting brain scans, and how sleep deprivation affects gene function by collecting samples of blood. By studying patients with depression who undergo total sleep deprivation, we may better understand how biological changes relate to rapid changes in depressive symptoms.

We aim to enroll 60 patients who have serious depression that has lasted for at least six months and who have not made any changes to current medication(s) for the past six weeks.

If you are eligible, your participation in the research may last approximately two weeks. During this time you will be required to make 2 separate visits to UCLA. Complete research study details can be found here.

This research study is being conducted with support from the UCLA Depression Grand Challenge and the National Institute of Mental Health Human Connectome Project (U01MH110008), which aims to acquire and share data about the structural and functional connectivity underlying human brain function as well as disease. For this reason, we will give access to some of the data, including MRI images and most behavioral data, to the general public via the internet. We will make all of the data, including data about your genes, available to other investigators that have been approved by the study researchers. Your data will be coded and will NOT have your name on it or any other personally identifying information. Letting us use and share your data is voluntary. However, you must be willing to share your data in this way in order to participate in this study. If you are not willing, you cannot participate in this research study.

Eligibility Requirements:

  • Have been experiencing a major depressive episode for at least 6 months.
  • Have not made any changes to current medications for the past 6 weeks.
  • Are between 20-64 years of age.
  • Are willing to receive several 2-hour MRI scans and several blood draws. Participants must comfortably fit in the MRI scanner, so height and weight will be collected during the phone screen to determine if this eligibility criteria has been met.
  • Able to pass a drug test and are willing to refrain from using any illicit substances, marijuana or cannabis in any form.
  • Not considered high risk for COVID-19 due to underlying medical conditions.

Process for determining eligibility:

  1. Initial eligibility will be determined by speaking with a study coordinator by phone, who will ask you questions about your medical history.
  2. If it appears that you may be eligible for the research study, we can schedule your consult visit to determine eligibility
  3. Note – if you are currently taking benzodiazepines, you must agree to refrain from taking them at least 72 hours prior to the sleep deprivation visit. If this is the case, we will also need a letter from your provider acknowledging your participation in the research study and plan to stop taking these medications for this period of time.
  4. If, after this initial Consult visit, it is determined that you meet all eligibility criteria, a study coordinator will schedule all of your remaining visits as soon as our schedule allows.

The researchers may end your participation in the study for a number of reasons, such as if your safety and welfare are at risk, if you do not follow instructions or if you miss scheduled visits.

If you are interested in speaking with a study coordinator to find out if you are potentially eligible for the study:

Please email DGCBiomarkerStudy@mednet.ucla.edu or call 310-825-4875 to speak to the Sleep Study Coordinator.

Research Protocol Details


If you are eligible, your participation in the research may last approximately one month. During this time, you will be required to make 2 separate visits to UCLA.

  • To determine if you are potentially eligible to participate in the study, you must first speak with a study coordinator by phone, who will ask you questions about your medical history. Time: Approximately 15 minutes.
  • If it appears that you may be eligible for the research study, we can schedule your initial appointment (Consult visit) to determine eligibility. If you are currently taking benzodiazepines, you will need to refrain from taking them at least 72 hours prior to the sleep deprivation visit. If this is the case, we will also need a letter from your provider acknowledging your participation in the research study and plan to stop taking these medications for this period of time.
  1. Consult: the first visit to determine eligibility will include a psychiatric evaluation, some standard blood and laboratory tests, an EKG, a urine sample, and detailed clinical mood evaluations. All portions of the Consult visit that do not require in-person interaction will be conducted while you are in a separate room but speaking via secure video conferencewith the research coordinator in a different room. The study doctors will need to review the results of these tests before deciding if you qualify for participating in the study. Time: Approximately 4 hours.
    • If you qualify, a study coordinator will then schedule all of your remaining visits as soon as our schedule allows.
      • These visits are based on the study physician, MRI scanner, and clinic availability, which are limited. Therefore, we do not have a lot of flexibility.
      • In general, sleep study visits are scheduled on Wednesday nights.
    • If you do not qualify, you will be notified by a study coordinator. As this is a research study, we have strict eligibility requirements, and exceptions cannot be made.
  2. Sleep Deprivation Session Visit: this visit will span two days and one night. You cannot drive yourself to/from this appointment. Time: Approximately 31 hours.
    • Day 1 of Sleep Deprivation Session Visit: During the first several hours of your visit, you will receive a brain MRI scan and complete some cognitive testing (if feasible at the time of assessment) and mood evaluations.
    • Overnight Sleep Deprivation: On the afternoon of Day 1, you will be checked into a research unit for overnight observation where you will be kept awake for the entire duration. During this time, you will complete mood surveys at regular intervals, and have an I/V line inserted into your arm to allow nurses to draw blood at 5 regular intervals. Follow the link for more details on the overnight sleep deprivation visit.
    • Day 2 of Sleep Deprivation Session Visit: You will receive a second brain MRI scan and complete some cognitive testing (if feasible at the time of assessment) and mood evaluations. You will receive compensation for your participation at the end of this visit.
  3. One week following your sleep deprivation session visit, you will be asked to complete a final survey, which will be sent to you via text message.

In total, if you are determined to be eligible for the research study, and you consent to participating in the research study - you will remain awake for approximately two days in our research center, and make 2 separate visits to UCLA. Your participation in this study will approximately be completed within two weeks.

Information about Total Sleep Deprivation


Below we include a summary of the use of total sleep deprivation in depression, potential adverse effects of total sleep deprivation, our study eligibility criteria, and major elements of the study protocol. Aspects of the study protocol will be implemented by UCLA research personnel, and not the patient’s psychiatrist or primary care physician.

The use of sleep deprivation in depression:
  • Total sleep deprivation has been shown for some people to produce a rapid antidepressant response within 24 hours.
  • Approximately 40-60% of patients who have undergone total sleep deprivation for a research study reported symptom improvements within 24-hours1-2.
  • The duration of symptom improvement is expected to be short, with relapse expected after recovery sleep, although some patients have reported that symptoms may be less severe following sleep recovery than prior to sleep deprivation3.
  • There is never a guarantee of response and currently no way to predict who might respond.
Additional Resources to read more about sleep deprivation for the treatment of depression:
Risks associated with sleep deprivation:
  • Total sleep deprivation is not considered a high-risk treatment intervention.
  • There is an increased risk of seizures in patients with a history of convulsions; for this reason, certain individuals are not eligible based on their medical and family history.
  • There is an increased risk of manic switching in patients with a history of switching while on mood stabilizers or rapid cycling; for this reason, certain individuals are not eligible.
  • Participants are unable to drive themselves home after the sleep deprivation study procedure.
Sleep Deprivation study procedure:
  • Sleep deprivation will be conducted in our clinical research laboratory at UCLA. For complete study visit details, see here.
  • After a full day of assessments, including an MRI brain scan, with our research staff, you will be checked into a research unit during the afternoon of Day 1 of the Sleep Deprivation study visit where you will be kept awake for the entire night.
  • During this time, you will complete mood evaluations at regular intervals.
  • A nurse will insert an I/V line into your arm to enable 5 separate blood sample draws at regular intervals over the course of the night.
  • You can read, watch movies, use a computer, talk to staff, and will be provided meals and snacks.
  • You will be required to remain upright under constant lighting conditions and will be prohibited from lying down or falling asleep.
  • You cannot leave the research unit or have visitors.
  • After 23 hours in the research unit, you will complete another set of assessments and MRI brain scan.
What to expect after after sleep deprivation?
  • Approximately half of patients report an improvement in symptoms within the time period that sleep deprivation occurs.
  • There is never a guarantee of response, or of knowing how long symptom improvement may last, and currently no way to predict who might respond.
  • If enrolled in this research study, and currently taking medication for depression, patients should continue to be closely monitored by their psychiatrists or primary care physicians to manage depressive symptoms whether or not they respond to sleep deprivation
References
  1. Benedetti, F., & Smeraldi, E. (2009). Neuroimaging and genetics of antidepressant response to sleep deprivation: implications for drug development. Curr Pharm Des, 15(22), 2637-2649.
  2. Gillin, J. C., Buchsbaum, M., Wu, J., Clark, C., & Bunney, W., Jr. (2001). Sleep deprivation as a model experimental antidepressant treatment: Findings from functional brain imaging. Depress Anxiety, 14(1), 37-49. doi:10.1002/da.1045 [pii]
  3. Giedke, H., & Schwarzler, F. (2002). Therapeutic use of sleep deprivation in depression. Sleep Med Rev, 6(5), 361-377

Magnetic Resonance Imaging (MRI) Brain Scan


Participation in this research study requires four separate MRI scans. Each MRI scan lasts up to 2 hours

You cannot receive an MRI scan if:

  • You have metal implants that contraindicate MRI scanning.
  • You experience claustrophobia that would prevent you from staying inside a narrow, confined space for up to two hours at a time
  • If female, you are pregnant or there is a possibility that you may be pregnant.

If you have metal implants, we require specific manufacturing information of these implants in order to determine MRI safety. Without this information, you will not be eligible.

Unlike a CT scan, a MRI scan does not use radiation. A MRI is essentially a big magnet that functions like a camera. For our study we are specifically looking at the brain. By taking pictures of your brain, before and after your infusions, we may better understand how ketamine affects brain chemistry and function. The scans for our study can last up to 2 hours. During that 2 hours, you will be lying flat and completely still during each scan; you will either be asked to rest with your eyes open, to perform some computer tasks while viewing images on a screen, or watch movie clips. Your head and upper torso will be inside a large tube, and you will remain inside for the entire duration of the scan. In order to ensure you remain as comfortable as possible, the study team will check in with you in between each scan, and we will offer you an optional break nearly half way through the scan.

MRI

FAQ


  • Do you need a letter from my provider before I can schedule the first consult visit?
  • If you are currently taking benzodiazepines, you will need to refrain from taking them at least 72 hours prior to the sleep deprivation visit. If this is the case, we will also need a letter from your provider acknowledging your participation in the research study and plan to stop taking these medications for this period of time. We will need to receive this letter before we can schedule your consult visit.

  • What medications are considered benzodiazepines?
  • Alprazolam (Xanax), Lorazepam (Ativan), Clonazepam (Klonopin), Oxazepam (Serax), Diazepam (Valium), Clobazam (Onfi), Clorazepate (Tranxene).

  • If I’ve been scheduled for my first consult visit, does that mean that I am eligible to participate in your research study?
  • No. We are only able to enroll people who have a certain history of depression and who can undergo brain scans and other procedures needed for the research. A study physician will review information collected during the first consult visit to determine if you are eligible to participate in the research study.

  • Why am I not eligible?
  • We are only able to enroll people who have a certain history of depression and who can undergo brain scans and other procedures needed for the research. You may talk to your doctor about treatment options for your depression. In addition, if you are at high risk for COVID-19 due to underlying medical conditions, you are not eligible to participate in the study.

  • Will I have access to the MRI and blood sample data?
  • No, this information is only used for research purposes.

  • Are there any weekend visits?
  • No, all of our in-person visits are scheduled on the weekdays.

  • What time does the overnight sleep deprivation visit start and when does it end?
  • You will arrive at UCLA at 11am and the next day you will be finished with the visit at 6:30pm.

  • I don’t live in Los Angeles, can I still be in the study?
  • You must live within a reasonable distance from UCLA (e.g., Orange County), be willing and able to come in for all study visits, and able to arrange transportation for all study visits.

  • Will I receive compensation and transportation reimbursements?
  • You may receive up to $700 for your participation in the research study. You will receive $20 per hour of your time for the consult interview and for completing all of the study visits. You will receive your first payment after you have completed the first consult interview, and again after you have completed your final research visit (at the end of sleep deprivation visit).

    You will be reimbursed for parking at UCLA. As you will not be allowed to drive yourself home after the sleep deprivation session, parking at UCLA for a responsible driver will be provided, or reimbursement up to $50 (to and from UCLA) will be provided.

    If you receive over $600 for your participation in the study, you will be required to complete a W-9 form for reporting the payment to the IRS. This will require that you provide a Social Security Number or Taxpayer Identification Number at the beginning of the study.

  • Who are the Principal Investigators of this study?
  • This study is being conducted by Eliza Congdon, PhD, Katherine Narr, PhD, and Randall Espinoza, MD, MPH, from the Departments of Psychiatry and Neurology at the University of California, Los Angeles (UCLA).

  • What if I have additional questions about my rights as a research subject?
  • Please call the UCLA Office Human Research Protection Program at (310) 825-5344.

Directions & Parking Information


If you have completed pre-screening by phone with a Sleep Study coordinator, have given us a letter from your Psychiatrist or Primary Care Provider acknowledging your participation in the study, and have been scheduled for your initial visit to determine eligibility – below are directions for your first visit.

Depression Grand Challenge Study Location:

740 Westwood Plaza, Los Angeles, CA 90095

From the San Diego Freeway (405):

From the north, exit Wilshire East, or from the south, exit Wilshire at Westwood. Turn left on Westwood Blvd. and go straight past Le Conte Avenue (the street becomes Westwood Plaza as you enter the UCLA campus).

The closest parking lot to Semel is Lot JS on Stein Plaza. (Entrance for parking can be seen below.) Parking permits at Stein Plaza are available for $13. You will be given a parking voucher at the end of your visit that is valid at Lot JS.

Parking spot

Once you park at Stein Plaza, walk North on Westwood Plaza. The UCLA Medical Plaza is on your left; the Semel Institute/Department of Psychiatry is on your right. If you reach the cross street Charles E. Young Dr. S, you have gone too far.

semel

The Semel Institute is in the Center for Health Sciences (CHS) Building – unfortunately it has a fairly confusing layout. Please see the map (below) for CHS for directions once you’re inside Semel:

  • Enter the Semel Institute from the west entrance on Westwood Plaza. (As seen below)
  • semel entrance
  • Walk all the way to the end of the hallway, turn left, then take your first right.
  • Take the H Elevators up to the 2nd floor
  • Look for the waiting room with glass doors as soon as you exit the elevator. A coordinator will meet you here at your appointment time.

Contact Us:


Please email DGCBiomarkerStudy@mednet.ucla.edu or call 310-825-4875 to speak to the Sleep Study Coordinator.

You may additionally contact the Principal Investigators, Dr. Katherine Narr at (310) 267-5119 or Dr. Eliza Congdon at econgdon@mednet.ucla.edu, with any questions or concerns about the research or your participation in this study.